Variant rs11243704 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000224140.6(SETX):c.6655-24G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 1,611,106 control chromosomes in the GnomAD database, including 102,533 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 17939 hom., cov: 30)

Exomes 𝑓: 0.32 ( 84594 hom. )

Consequence

SETX
ENST00000224140.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.881

Variant links:

Genes affected

SETX (HGNC:445): (senataxin) This gene encodes a protein named for its homology to the Sen1p protein of fungi which has RNA helicase activity encoded by a domain at the C-terminal end of the protein. The protein encoded by this gene contains a DNA/RNA helicase domain at its C-terminal end which suggests that it may be involved in both DNA and RNA processing. Mutations in this gene have been associated with ataxia-ocular apraxia-2 (AOA2) and an autosomal dominant form of juvenile amyotrophic lateral sclerosis (ALS4). [provided by RefSeq, Jul 2008]

SETX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 9-132278281-C-T is Benign according to our data. Variant chr9-132278281-C-T is described in ClinVar as [Benign]. Clinvar id is 260513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-132278281-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SETX	NM_015046.7 linkuse as main transcript	c.6655-24G>A		intron_variant		ENST00000224140.6	NP_055861.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SETX	ENST00000224140.6 linkuse as main transcript	c.6655-24G>A		intron_variant		1	NM_015046.7	ENSP00000224140	P1	Q7Z333-1
SETX	ENST00000436441.5 linkuse as main transcript	c.1381-24G>A		intron_variant		5		ENSP00000409143

Frequencies

GnomAD3 genomes

AF:

0.442

AC:

67058

AN:

151646

Hom.:

17894

Cov.:

show subpopulations

Gnomad AFR

AF:

0.745

Gnomad AMI

AF:

0.201

Gnomad AMR

AF:

0.345

Gnomad ASJ

AF:

0.407

Gnomad EAS

AF:

0.699

Gnomad SAS

AF:

0.453

Gnomad FIN

AF:

0.292

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.289

Gnomad OTH

AF:

0.416

GnomAD3 exomes

AF:

0.378

AC:

94805

AN:

251016

Hom.:

20899

AF XY:

0.374

AC XY:

50713

AN XY:

135678

show subpopulations

Gnomad AFR exome

AF:

0.755

Gnomad AMR exome

AF:

0.289

Gnomad ASJ exome

AF:

0.396

Gnomad EAS exome

AF:

0.715

Gnomad SAS exome

AF:

0.440

Gnomad FIN exome

AF:

0.296

Gnomad NFE exome

AF:

0.294

Gnomad OTH exome

AF:

0.355

GnomAD4 exome

AF:

0.321

AC:

469136

AN:

1459342

Hom.:

84594

Cov.:

AF XY:

0.325

AC XY:

235758

AN XY:

726154

show subpopulations

Gnomad4 AFR exome

AF:

0.762

Gnomad4 AMR exome

AF:

0.295

Gnomad4 ASJ exome

AF:

0.393

Gnomad4 EAS exome

AF:

0.723

Gnomad4 SAS exome

AF:

0.436

Gnomad4 FIN exome

AF:

0.300

Gnomad4 NFE exome

AF:

0.282

Gnomad4 OTH exome

AF:

0.371

GnomAD4 genome

AF:

0.443

AC:

67157

AN:

151764

Hom.:

17939

Cov.:

AF XY:

0.442

AC XY:

32783

AN XY:

74154

show subpopulations

Gnomad4 AFR

AF:

0.745

Gnomad4 AMR

AF:

0.345

Gnomad4 ASJ

AF:

0.407

Gnomad4 EAS

AF:

0.698

Gnomad4 SAS

AF:

0.453

Gnomad4 FIN

AF:

0.292

Gnomad4 NFE

AF:

0.289

Gnomad4 OTH

AF:

0.415

Alfa

AF:

0.337

Hom.:

4341

Bravo

AF:

0.462

Asia WGS

AF:

0.565

AC:

1967

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 03, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Amyotrophic lateral sclerosis type 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Feb 08, 2023

- -

Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Feb 08, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.052

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over